The major goals of this project are to isolate and purify fibroblast chemoattractants and to study the biochemical and physiological events associated with their interaction with the fibroblast plasma membrane. We will determine whether lymphocyte-derived chemotactic factor for fibroblasts (LDCF-F), complement-derived chemotactic factor for fibroblasts (C5-DCF) and chemotactic matrix molecules (collagen, collagen-derived peptides, and fibronectin are able to stimulate fibroblasts to increase or decrease collagen glycosaminoglycan and collagenase synthesis. We will isolate and purify the lymphokine(s) responsible for stimulating fibroblasts to synthesize collagen and collagenase and determine whether activation of complement in the serum generates any complement split product capable of stimulating synthesis of collagen, GAG or collagenase by the fibroblast. Collagen synthesis by fibroblasts will be measured by the degree of incorporation of (14C) proline into collagenase sensitive protein (collagen). GAG synthesis will be measured by the degree of incorporation of 35SNa2SO4 into proteins (glycosaminoglycans). Collagenase activity will be quantitated by determining the rate of lysis of 14C labeled collagen substrate. The role that protein carboxymethylation and phosphorylation reactions and cyclic nucleotides play in fibroblast chemotaxis and metabolic activation will be studied. The importance of monovalent and divalent cations in fibroblast chemotaxis and metabolic activation will also be assessed. The mechanism(s) by which fibroblast migration and metabolism is modulated during different states of morphogenesis and at sites of tissue injury and repair in vivo are incompletely understood at present. This proposal attempst to study these mechanisms by working with specific, isolated and purified substances which can modulate fibroblast chemotaxis and metabolism in vitro and determine whether the same substances can be recovered from sites of well defined inflammatory reactions in vivo.